tbuckley/cabot-search huggingface dataset:
Polymeric nanocarriers for nose-to-brain drug delivery in neurodegenerative diseases and neurodevelopmental disorders
Authors: Rania Awad, Avi Avital, Alejandro Sosnik
Journal: Acta Pharmaceutica Sinica B (2022)

Neurodegenerative diseases are progressive conditions that affect the neurons of the central nervous system (CNS) and result in their damage and death. Neurodevelopmental disorders include intellectual disability, autism spectrum disorder, and attention-deficit/hyperactivity disorder and stem from the disruption of essential neurodevelopmental processes. The treatment of neurodegenerative and neurodevelopmental conditions, together affecting ∼120 million people worldwide, is challenged by the blood–brain barrier (BBB) and the blood–cerebrospinal fluid barrier that prevent the crossing of drugs from the systemic circulation into the CNS. The nose-to-brain pathway that bypasses the BBB and increases the brain bioavailability of intranasally administered drugs is promising to improve the treatment of CNS conditions. This pathway is more efficient for nanoparticles than for solutions, hence, the research on intranasal nano-drug delivery systems has grown exponentially over the last decade. Polymeric nanoparticles have become key players in the field owing to the high design and synthetic flexibility. This review describes the challenges faced for the treatment of neurodegenerative and neurodevelopmental conditions, the molecular and cellular features of the nasal mucosa and the contribution of intranasal nano-drug delivery to overcome them. Then, a comprehensive overview of polymeric nanocarriers investigated to increase drug bioavailability in the brain is introduced.
Insights on the molecular targets of cardiotoxicity induced by anticancer drugs: A systematic review based on proteomic findings
Authors: Sofia Reis Brandão, Félix Carvalho, Francisco Amado, Rita Ferreira, Vera Marisa Costa
Journal: Metabolism (2022)

Several anticancer agents have been associated with cardiac toxic effects. The currently proposed mechanisms to explain cardiotoxicity differ among anticancer agents, but in fact, the specific modulation is not completely elucidated. Thus, this systematic review aims to provide an integrative perspective of the molecular mechanisms underlying the toxicity of anticancer agents on heart muscle while using a high-throughput technology, mass spectrometry (MS)-based proteomics. A literature search using PubMed database led to the selection of 27 studies, of which 13 reported results exclusively on animal models, 13 on cardiomyocyte-derived cell lines and only one included both animal and a cardiomyocyte line. The reported anticancer agents were the proteasome inhibitor carfilzomib, the anthracyclines daunorubicin, doxorubicin, epirubicin and idarubicin, the antimicrotubule agent docetaxel, the alkylating agent melphalan, the anthracenedione mitoxantrone, the tyrosine kinase inhibitors (TKIs) erlotinib, lapatinib, sorafenib and sunitinib, and the monoclonal antibody trastuzumab. Regarding the MS-based proteomic approaches, electrophoretic separation using two-dimensional (2D) gels coupled with tandem MS (MS/MS) and liquid chromatography-MS/MS (LC-MS/MS) were the most common. Overall, the studies highlighted 1826 differentially expressed proteins across 116 biological processes. Most of them were grouped in larger processes and critically analyzed in the present review. The selection of studies using proteomics on heart muscle allowed to obtain information about the anticancer therapy-induced modulation of numerous proteins in this tissue and to establish connections that have been disregarded in other studies. This systematic review provides interesting points for a comprehensive understanding of the cellular cardiotoxicity mechanisms of different anticancer drugs.
Adipose tissue and ovarian aging: Potential mechanism and protective strategies
Authors: Meng Wu, Yibao Huang, Qingqing Zhu, Xiaoran Zhu, Liru Xue, Jiaqiang Xiong, Ying Chen, Chuqing Wu, Yican Guo, Yinuo Li, Mingfu Wu, Shixuan Wang
Journal: Ageing Research Reviews (2022)
Reply
Authors: Hui Li, Chang Liu, Hong Wu
Journal: Hepatology (2022)

We thank for Dr. Wang for his comment on our recent study.1 In this study, we focused on identification of an IL‐6‐induced circular RNA (circRNA)–circRNA derived from gametogenetin binding protein 2 (cGGNBP2) and its biological function in intrahepatic cholangiocarcinoma (ICC). We found that cGGNBP2 could encode the protein cGGNBP2‐184aa and that IL‐6/cGGNBP2‐184aa/signal transducer and activator of transcription 3 formed a positive feedback loop to facilitate ICC progression. We agree that the cellular roles of circRNA are complex: modulating transcription; regulating splicing, platforms, or sponges for proteins and sponges for microRNAs (miRNAs); interacting with mRNAs; and translating proteins.2,3 Through reviewing the published works concerning the biological functions of circRNAs, most of the known circRNAs were identified as sponges for miRNAs. By stating "Most circRNAs have been proposed to function as a microRNA sponge or protein scaffold," we did not mean that the main function of circRNAs was sponging miRNAs and protein scaffolds. Indeed, binding sites are necessary for miRNA sponging. In our study, we focused on the translational capability of cGGNBP2 and did not detect the miRNA binding sites. As shown in the paper, we have demonstrated that cGGNBP2 exerts its biological function mainly by translating the protein cGGNBP2‐184aa. Overexpression of cGGNBP2‐184aa markedly increased the growth and invasive capability of ICC cells. However, overexpression of internal ribosome entry site–mutated vectors (by which cGGNBP2 RNA levels could be dramatically elevated, while cGGNBP2‐184aa could not) did not influence the function of ICC cells. This suggested partly that cGGNBP2 might not exert its biological function by sponging miRNAs or proteins. However, further work should be performed to confirm this. In conclusion, we appreciate the comment by Dr. Wang that a comprehensive work should be performed when we discuss the biological function of circRNAs as miRNA sponges.
Corrigendum to “Corrigendum to ‘Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up’”
Authors: M.A. Dimopoulos, P. Moreau, E. Terpos, M.V. Mateos, S. Zweegman, G. Cook, M. Delforge, R. Hájek, F. Schjesvold, M. Cavo, H. Goldschmidt, T. Facon, H. Einsele, M. Boccadoro, J. San-Miguel, P. Sonneveld, U. Mey
Journal: Annals of Oncology (2022)
Application of Improved Robot-assisted Laparoscopic Telesurgery with 5G Technology in Urology
Authors: Jianmin Li, Xuecheng Yang, Guangdi Chu, Wei Feng, Xuemei Ding, Xulong Yin, Liangjun Zhang, Wei Lv, Lufei Ma, Liguo Sun, Run Feng, Jun Qin, Xuefeng Zhang, Chengyi Gou, Zongyi Yu, Bin Wei, Wei Jiao, Yonghua Wang, Lei Luo, Hang Yuan, Yuan Chang, Qiliang Cai, Shuxin Wang, Pier Cristoforo Giulianotti, Qian Dong, Haitao Niu
Journal: European Urology (2022)
Complex genomic rearrangements: an underestimated cause of rare diseases
Authors: Jakob Schuy, Christopher M. Grochowski, Claudia M.B. Carvalho, Anna Lindstrand
Journal: Trends in Genetics (2022)

Complex genomic rearrangements (CGRs) are known contributors to disease but are often missed during routine genetic screening. Identifying CGRs requires (i) identifying copy number variants (CNVs) concurrently with inversions, (ii) phasing multiple breakpoint junctions incis, as well as (iii) detecting and resolving structural variants (SVs) within repeats. We demonstrate how combining cytogenetics and new sequencing methodologies is being successfully applied to gain insights into the genomic architecture of CGRs. In addition, we review CGR patterns and molecular features revealed by studying constitutional genomic disorders. These data offer invaluable lessons to individuals interested in investigating CGRs, evaluating their clinical relevance and frequency, as well as assessing their impact(s) on rare genetic diseases.
Breakthrough SARS-CoV-2 infections during periods of delta and omicron predominance, South Africa
Authors: Ameena Goga, Linda-Gail Bekker, Nigel Garrett, Tarylee Reddy, Nonhlanhla Yende-Zuma, Lara Fairall, Harry Moultrie, Azwidihwi Takalani, Valentina Trivella, Mark Faesen, Veronique Bailey, Ishen Seocharan, Glenda E Gray
Journal: The Lancet (2022)
Effect of El Niño–Southern Oscillation and local weather on Aedes vector activity from 2010 to 2018 in Kalutara district, Sri Lanka: a two-stage hierarchical analysis
Authors: Prasad Liyanage, Yesim Tozan, Hans J Overgaard, Hasitha Aravinda Tissera, Joacim Rocklöv
Journal: The Lancet Planetary Health (2022)

BackgroundDengue, transmitted by Aedes mosquitoes, is a major public health problem in Sri Lanka. Weather affects the abundance, feeding patterns, and longevity of Aedes vectors and hence the risk of dengue transmission. We aimed to quantify the effect of weather variability on dengue vector indices in ten Medical Officer of Health (MOH) divisions in Kalutara, Sri Lanka.MethodsMonthly weather variables (rainfall, temperature, and Oceanic Niño Index [ONI]) and Aedes larval indices in each division in Kalutara were obtained from 2010 to 2018. Using a distributed lag non-linear model and a two-stage hierarchical analysis, we estimated and compared division-level and overall relationships between weather and premise index, Breteau index, and container index.FindingsFrom Jan 1, 2010, to Dec 31, 2018, three El Niño events (2010, 2015–16, and 2018) occurred. Increasing monthly cumulative rainfall higher than 200 mm at a lag of 0 months, mean temperatures higher than 31·5°C at a lag of 1–2 months, and El Niño conditions (ie, ONI >0·5) at a lag of 6 months were associated with an increased relative risk of premise index and Breteau index. Container index was found to be less sensitive to temperature and ONI, and rainfall. The associations of rainfall and temperature were rather homogeneous across divisions.InterpretationBoth temperature and ONI have the potential to serve as predictors of vector activity at a lead time of 1–6 months, while the amount of rainfall could indicate the magnitude of vector prevalence in the same month. This information, along with knowledge of the distribution of breeding sites, is useful for spatial risk prediction and implementation of effective Aedes control interventions.FundingNone.
Assessing microstructural critical quality attributes in PLGA microspheres by FIB-SEM analytics
Authors: Andrew G. Clark, Ruifeng Wang, Yuri Qin, Yan Wang, Aiden Zhu, Joshua Lomeo, Quanying Bao, Diane J. Burgess, Jacie Chen, Bin Qin, Yuan Zou, Shawn Zhang
Journal: Journal of Controlled Release (2022)
Letter to the editor: The limited function of most circRNAs as a microRNA sponge
Authors: Ye‐Zhao Wang
Journal: Hepatology (2022)

To the editor, I read the article by Li et al.1 focusing on understanding the underlying oncogenic functions and probable tumorigenesis‐promoting mechanisms of the cGGNBP2‐184aa (a protein encoded by an IL‐6–induced circular RNA [circRNA] gametogenetin‐binding protein 2 [GGNBP2], derived from ggnbp2, from exons 3–6 of the circRNA termed as cGGNBP2)–IL‐6–STAT3 signaling axis and their interaction with RNA‐binding protein DEx‐H Box Helicase 9, as well as applications of cGGNBP2 as an independent risk factor in intrahepatic cholangiocarcinoma (ICC) prognosis, and that cGGNBP2‐184aa may serve as an auxiliary target for clinical IL‐6/STAT3‐targeting treatments in ICC. Although cGGNBP2 will play an important role and have a promising clinical application value, there is a misunderstanding regarding a biological function of most circRNA as a microRNA (miRNA) sponge in this manuscript, and I believe the article by Li et al. overlooks the limited function of most circRNAs as a miRNA sponge. The authors primarily discuss one reported biological function of most circRNAs as sponging of miRNAs.1 In their article, the authors state that circRNAs function mostly by "sponging" miRNAs and have made some strong comments: "Conventionally, circRNAs were considered as noncoding RNAs because of a lack of 5′cap as well as 3′end structure and exerted their functions mainly as microRNA sponge and protein scaffold,"1 and, "the biological functions of circRNAs have been intensively described in various cancers. Most circRNAs have been proposed to function as a microRNA sponge or protein scaffold."1 However, in theory, a sponge must have several binding sites for miRNAs to be a "sponge." It was already published in 2014 by Guo et al. that following this concept, only the minority of circRNAs are true sponges for miRNAs.2,3 Indeed, it was also reported that most circRNAs, which are much less abundant than miRNAs, were not predicted to "function as a miRNA sponge nearly as effectively as CDR1as [defined as antisense transcript of the cerebellar degeneration related protein 1, one of the best‐known and most well‐described circRNAs]."2 In addition, it should be noted that the majority of circRNAs in mammals rarely contain multiple binding sites for the same miRNAs [also known as miRNA response elements, miRNA recognition elements, and/or miRNA‐binding sites].3 Therefore, the authors should discuss the limited function of circRNAs as a miRNA sponge and provide more details about the clinical significance of miRNA sponges.
Transforming food systems with trees and forests
Authors: Amy Ickowitz, Stepha McMullin, Todd Rosenstock, Ian Dawson, Dominic Rowland, Bronwen Powell, Kai Mausch, Houria Djoudi, Terry Sunderland, Mulia Nurhasan, Andreea Nowak, Vincent Gitz, Alexandre Meybeck, Ramni Jamnadass, Manuel R Guariguata, Céline Termote, Robert Nasi
Journal: The Lancet Planetary Health (2022)
Physical activity, diet quality and all-cause cardiovascular disease and cancer mortality: a prospective study of 346 627 UK Biobank participants
Authors: Ding Ding, Joe Van Buskirk, Binh Nguyen, Emmanuel Stamatakis, Mona Elbarbary, Nicola Veronese, Philip J Clare, I-Min Lee, Ulf Ekelund, Luigi Fontana
Journal: British Journal of Sports Medicine (2022)

Objectives To examine independent and interactive associations of physical activity and diet with all-cause, cardiovascular disease (CVD) and physical activity, diet and adiposity-related (PDAR) cancer mortality. Methods This population-based prospective cohort study (n=346 627) is based on the UK Biobank data with linkage to the National Health Service death records to 30 April 2020. A left-truncated Cox proportional hazards model was fitted to examine the associations between exposures (self-reported total moderate-to-vigorous intensity physical activity (MVPA), vigorous-intensity physical activity (VPA) and a diet quality index (score ranged 0–3)) and outcomes (all-cause, CVD and PDAR cancer mortality). Results During a median follow-up of 11.2 years, 13 869 participants died from all causes, 2650 from CVD and 4522 from PDAR cancers. Compared with quartile 1 (Q1, 0–210 min/week), Q2–Q4 of MVPA were associated with lower risks of all-cause (HR ranged from 0.87 (95% CI: 0.83 to 0.91) to 0.91 (95% CI: 0.87 to 0.96)), CVD (HR ranged from 0.85 (95% CI: 0.76 to 0.95) to 0.90 (95% CI: 0.81 to 1.00)) and PDAR cancer mortality (HR ranged from 0.86 (95% CI: 0.79 to 0.93) to 0.94 (95% CI: 0.86 to 1.02)). Compared with no VPA, any VPA was associated with lower risk for all-cause and CVD mortality (HR ranged from 0.85 (95% CI: 0.80 to 0.89) to 0.88 (95% CI: 0.84 to 0.93) and from 0.75 (95% CI: 0.68 to 0.83) to 0.90 (95% CI: 0.80 to 1.02), respectively). Although not reaching statistical significance for all-cause and CVD mortality, being in the best dietary category (diet quality index=2–3) was associated with a reduction in PDAR cancer mortality (HR=0.86, 95% CI: 0.78 to 0.93). No additive or multiplicative interactions between physical activity categories and dietary quality was found. When comparing across physical activity and diet combinations, the lowest risk combinations consistently included the higher levels of physical activity and the highest diet quality score. Conclusions Adhering to both quality diet and sufficient physical activity is important for optimally reducing the risk of mortality from all causes, CVD and PDAR cancers.
Risk of acute liver injury following the mRNA (BNT162b2) and inactivated (CoronaVac) COVID-19 vaccines
Authors: Carlos King Ho Wong, Lung Yi Mak, Ivan Chi Ho Au, Francisco Tsz Tsun Lai, Xue Li, Eric Yuk Fai Wan, Celine Sze Ling Chui, Esther Wai Yin Chan, Wing Yiu Cheng, Franco Wing Tak Cheng, Man Fung Yuen, Ian Chi Kei Wong
Journal: Journal of Hepatology (2022)
Radical treatment for blastomycosis following unsuccessful liposomal amphotericin
Authors: Christopher Chew, Nikhilesh Thapa, Henry Ogbuagu, Merin Varghese, Dhaval Patel, Raza Abbas, Jason Oh, Molla Teshome, Khaja Mohammed, Sohail Saleem, Deepak Aggarwal, Barry Barns, April McDonald, Claudia Ormenisan-Gherasim
Journal: The Lancet Infectious Diseases (2022)
PCSK9 and ANGPTL3 levels correlate with hyperlipidemia in HIV-lipoatrophy, are regulated by fasting and are not affected by leptin administered in physiologic or pharmacologic doses
Authors: Eirini Bouzoni, Nikolaos Perakakis, Margery A Connelly, Angeliki M Angelidi, Eleni Pilitsi, Olivia Farr, Konstantinos Stefanakis, Christos S Mantzoros
Journal: Metabolism (2022)
Vitamin B12 and folate decrease inflammation and fibrosis in NASH by preventing syntaxin 17 homocysteinylation
Authors: Madhulika Tripathi, Brijesh Kumar Singh, Jin Zhou, Keziah Tikno, Anissa Widjaja, Reddemma Sandireddy, Kabilesh Arul, Siti Aishah Binte Abdul Ghani, George Goh Boon Bee, Kiraely Adam Wong, Ho Jia Pei, Shamini Guna Shekeran, Rohit Anthony Sinha, Manvendra K. Singh, Stuart Alexander Cook, Ayako Suzuki, Teegan Reina Lim, Chang-Chuen Cheah, Jue Wang, Rui-Ping Xiao, Xiuqing Zhang, Pierce Kah Hoe Chow, Paul Michael Yen
Journal: Journal of Hepatology (2022)

Several recent clinical studies have shown that serum homocysteine (Hcy) levels are positively correlated, while vitamin B12 (B12) and folate levels are negative correlated, with non-alcoholic steatohepatitis (NASH) severity. However, it is not known whether hyperhomocysteinemia (HHcy) plays a pathogenic role in NASH.We examined the effects of HHcy on NASH progression, metabolism, and autophagy in dietary and genetic mouse models, patients, and primates. We employed vitamin B12 (B12) and folate (Fol) to reverse NASH features in mice and cell culture.Serum Hcy correlated with hepatic inflammation and fibrosis in NASH. Elevated hepatic Hcy induced and exacerbated NASH. Gene expression of hepatic Hcy-metabolizing enzymes was downregulated in NASH. Surprisingly, we found increased homocysteinylation (Hcy-lation) and ubiquitination of multiple hepatic proteins in NASH including the key autophagosome/lysosome fusion protein, Syntaxin 17 (Stx17). This protein was Hcy-lated and ubiquitinated, and its degradation led to a block in autophagy. Genetic manipulation of Stx17 revealed its critical role in regulating autophagy, inflammation and fibrosis during HHcy. Remarkably, dietary B12/Fol, which promotes enzymatic conversion of Hcy to methionine, decreased HHcy and hepatic Hcy-lated protein levels, restored Stx17 expression and autophagy, stimulated β -oxidation of fatty acids, and improved hepatic histology in mice with pre-established NASH.HHcy plays a key role in the pathogenesis of NASH via Stx17 homocysteinylation. B12/folate also may represent a novel first-line therapy for NASH.The incidence of non-alcoholic steatohepatitis, for which there are no approved pharmacological therapies, is increasing, posing a significant healthcare challenge. Herein, based on studies in mice, primates and humans, we found that dietary supplementation with vitamin B12 and folate could have therapeutic potential for the prevention or treatment of non-alcoholic steatohepatitis.
Acyl-CoA:diacylglycerol acyltransferase: Properties, physiological roles, metabolic engineering and intentional control
Authors: Guanqun Chen, John L. Harwood, M. Joanne Lemieux, Scot J. Stone, Randall J. Weselake
Journal: Progress in Lipid Research (2022)

Acyl-CoA:diacylglycerol acyltransferase (DGAT, EC 2.3.1.20) catalyzes the last reaction in the acyl-CoA-dependent biosynthesis of triacylglycerol (TAG). DGAT activity resides mainly in DGAT1 and DGAT2 in eukaryotes and bifunctional wax ester synthase-diacylglycerol acyltransferase (WSD) in bacteria, which are all membrane-bound proteins but exhibit no sequence homology to each other. Recent studies also identified other DGAT enzymes such as the soluble DGAT3 and diacylglycerol acetyltransferase (EaDAcT), as well as enzymes with DGAT activities including defective in cuticular ridges (DCR) and steryl and phytyl ester synthases (PESs). This review comprehensively discusses research advances on DGATs in prokaryotes and eukaryotes with a focus on their biochemical properties, physiological roles, and biotechnological and therapeutic applications. The review begins with a discussion of DGAT assay methods, followed by a systematic discussion of TAG biosynthesis and the properties and physiological role of DGATs. Thereafter, the review discusses the three-dimensional structure and insights into mechanism of action of human DGAT1, and the modeled DGAT1 from Brassica napus. The review then examines metabolic engineering strategies involving manipulation of DGAT, followed by a discussion of its therapeutic applications. DGAT in relation to improvement of traits of farmed animals is also discussed along with DGATs in various other eukaryotic organisms.
ICG-mediated photodisruption of the inner limiting membrane enhances retinal drug delivery
Authors: Karen Peynshaert, Helena Vanluchene, Kaat De Clerck, An-Katrien Minnaert, Morgane Verhoeven, Noémie Gouspillou, Nezahat Bostan, Toshio Hisatomi, Geraldine Accou, Félix Sauvage, Kevin Braeckmans, Stefaan De Smedt, Katrien Remaut
Journal: Journal of Controlled Release (2022)